Dermatomyositis (DM) is a severe autoimmune connective tissue disease in which patients routinely endure prolonged courses of systemic treatments that are associated with significant toxicity for their skin disease. Although over 60,000 individuals have DM in the U.S., the majority of whom have skin findings, there have been no prospective studies of treatments for the many patients with skin predominant disease. The goal of this proposal is to initiate a short-term (12 week treatment) clinical study to examine the role of ajulemic acid for patients with refractory dermatomyositis (DM) involving the skin. Patients with skin manifestations of dermatomyositis have extremely poor quality of life, including severe pruritus and depression, and current therapies are frequently ineffective. First line treatment for the skin is antimalarials, which frequently are not effective or cause drug reactions. We propose a randomized placebo-controlled clinical trial in DM patients with refractory skin disease, to test the safety and explore the clinical efficacy of ajulemic acid (AjA, a synthetic, nonpsychoactive, anti-inflammatory, analgesic cannabinoid, compared to placebo for the treatment of skin disease associated with DM. We anticipate that results from the proposed clinical trial will be used to power a larger Phase II clinical trial for clinical efficac of AjA. To test biological efficacy of AjA, serum levels and PBMC production of IL-1?, IFN?, IFN?, TNF?, and expression in PBMC of the IFN? signature will be examined before and after dosing. Successful completion of these studies should also allow us to determine biomarker endpoints for clinical efficacy to be used in a larger clinical trial. There is a great need for new approachs to treatment of the skin lesions of patients with dermatomyositis. This clinical study will allow careful observation of a potentially exciting new treatment.